Approximately one third of terminally ill AIDS patients develop severe cognitive deficits called HIV-associated dementi complex (HIV-ADC). As the efficacy of chemoprophylaxis for opportunistic infections and systemic control HIV replication are improved, survival would be expected to increase and thus the incidence of HIV-ADC would also be expected to increase and lead to greater morbidity. It is the consensus of opinion that HIV does not directly mediate neuronal damage by infecting neuroglial cells. Unfortunately, that is where the consensus ends. We are interested in studying the pathogenesis of neurologic damage associated with HIV encephalitis, a known pathologic substrate of ADC. Most hypotheses of the pathogenesis of neurologic damage in HIV encephalitis focus on neurotoxic HIV proteins or immune factors. This grant is examining the latter. There are numerous candidate immune factors in AIDS that could mediate neurologic disease. Given the character of the histopathology, macrophage factors deserve the greatest attention. As a beginning, we have chosen to perform a detailed analysis of 4 cytokines that have the potential to mediate neurotoxicity. Using well characterized autopsy tissues, we will define cytokine abundance and message expression in select regions of the CNS. For cytokines to have an affect, they must bind to specific membrane receptors. We will characterize the distribution of these receptors within the CNS of control and AIDS brains. We will then compare the distribution of the cytokines and their receptors to the presence of HIV infection and associated neurologic damage. Lastly, we will develop an in vitro system that can assess the presence of these cytokines in primary CNS cultures that, in the future, could be used to examine the pathogenesis of HIV encephalitis and the effects of interrupting cytokine pathways in the progression of neurologic damage. For cytokines to have an effect, they must bind to specific membrane receptors. We will characterize the distribution of these receptors within the CNS of control and AIDS brains.